Search Results (2,179)

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline, synaptic loss, and multifaceted pathology involving amyloid-β (Aβ) aggregation, tau hyperphosphorylation, neuroinflammation, and impaired proteostasis. In recent years, biologic therapies, such as monoclonal antibodies, vaccines, antisense oligonucleotides (ASOs), and gene therapies, have gained prominence as promising disease-modifying strategies. In this review, we provide a comprehensive synthesis of current biologic approaches under clinical evaluation for AD. Drawing on data curated from ClinicalTrials.gov (as of 2025), we systematically summarise the molecular targets, therapeutic modalities, mechanisms of action, trial phases, and sponsors of over 60 biologic agents. These include Aβ-directed antibodies targeting distinct conformers such as protofibrils, pyroglutamate-modified species, and soluble oligomers; tau-targeted immunotherapies and RNA-based interventions; and emerging platforms focused on neuroimmune modulation, peptide hormones, and microbiota-based strategies. Gene and RNA therapeutics, particularly ASOs and small interfering RNAs (siRNAs) delivered intrathecally or via lipid nanoparticles, are also reviewed for their potential to modulate intracellular targets with high specificity. We also analyse the historical landscape of biologic candidates that failed to reach approval, discussing key reasons for trial discontinuation, including lack of clinical efficacy, safety concerns (e.g., amyloid-related imaging abnormalities), or inadequate biomarker responses. These cases offer crucial insights for refining future drug design. Looking ahead, we highlight major challenges and evolving perspectives in AD biologic therapy: expanding therapeutic targets beyond Aβ and tau, overcoming delivery barriers to the brain, designing prevention-oriented and genetically stratified trials, and navigating regulatory and ethical considerations. Together, these efforts signal a paradigm shift in AD drug development, from symptomatic treatment to mechanism-based precision biologics. By integrating real-time clinical trial data with mechanistic insight, this review aims to inform both translational research and therapeutic innovation in AD. Full article

Survivin, a pivotal member of the inhibitor of apoptosis proteins (IAP) family, plays critical roles in cell cycle regulation and division. Survivin is overexpressed in most malignancies, making it an attractive therapeutic target. Due to its high specificity and potency, siRNA-based RNA interference (RNAi) has emerged as a powerful therapeutic strategy for effectively downregulating disease-related genes such as survivin in cancer therapy. However, naked siRNA suffers from rapid enzymatic degradation, poor cellular uptake, and off-target effects, severely limiting its therapeutic efficacy in vivo. Development of polymer-based nanocarriers for tumor-targeted delivery of survivin siRNA (siSurvivin) holds great potential to address these challenges. In this review, we first described the structure and function of survivin and summarized the survivin-targeted therapeutic strategy. Then, the siRNA delivery systems, particularly the polymeric nanocarriers, were introduced. Furthermore, a plethora of polymer-based nanocarriers for tumor-targeted siSurvivin delivery, including synthetic polymers (branched polymers, dendritic polymers, polymeric micelles), natural polymers (polysaccharides, proteins, and others), lipid-polymer hybrid nanoparticles, and polymer composite nanoparticles, were elaborated. Promising results underscore the potential of polymer-based nanocarriers for survivin siRNA delivery to enhance cancer therapy, providing a roadmap for future clinical translation. Full article

MRNA-based therapeutics and vaccines represent a rapidly expanding frontier in biomedical innovation, with lipid nanoparticles (LNPs) serving as a clinically validated delivery platform. This study explores critical quality attributes of LNP-mRNA formulations, with a particular focus on in vitro biological activity, a key quality attribute of vaccine activity and batch-to-batch consistency. We discuss the importance of optimizing both LNP components and mRNA structure, highlighting recent advances in formulation strategies. Furthermore, we examine the influence of factors such as cell-line selection, experimental design, storage conditions, and targeted cellular delivery on transduction efficiency. Our findings underscore the need for standardized in vitro assays and process-integrated monitoring to support the scalable development and regulatory assessment of mRNA-based therapies. Full article

Lung cancer remains a foremost cause of cancer-related impermanence globally, demanding innovative and effective therapeutic strategies. Polymeric nanoparticles (NPs) have turned up as a promising transport system for drugs due to their biodegradability, biocompatibility, and capability to provide controlled and targeted release of therapeutic agents. This review offers a thorough examination of different polymeric NP platforms, such as chitosan, gelatin, alginate, poly (lactic acid), and polycaprolactone, highlighting their mechanisms, formulations, and applications in the treatment of lung cancer. These NPs facilitate the delivery of chemotherapeutic agents, gene therapies, and immune modulators, with enhanced bioavailability and reduced systemic toxicity. Additionally, advanced formulations such as ligand-conjugated, stimuli-responsive, and multifunctional NPs demonstrate improved tumor-specific accumulation and cellular uptake. The review also discusses quantum dots, magnetic and lipid-based NPs, and green-synthesized metallic polymeric hybrids, emphasizing their potential in theranostics and combination therapies. Preclinical studies show promising results, yet clinical translation faces challenges; for example, large-scale production, long-term toxicity, and regulatory hurdles. Overall, polymeric NPs represent a powerful platform for advancing personalized lung cancer therapy, with future prospects rooted in multifunctional, targeted, and patient-specific nanomedicine. Full article

Background: Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. The RABV glycoprotein (RABV-G) serves as the key antigen for eliciting protective immunity. Methods: We developed a novel QS21+CpG-adjuvanted RABV-G subunit vaccine and systematically compared its performance against three control formulations: mRNA vaccine composed of H270P-targeted mutation packaged in lipid nanoparticles (LNP), named LNP-mRNA-G-H270P, commercial inactivated vaccine, and alum-adjuvanted RABV-G subunit vaccine. Results: The result show that the G+QS21+CpG subunit vaccine elicited superior humoral immunity, as evidenced by significantly higher RABV-G-specific IgG titers and virus-neutralizing antibody responses compared to all other groups. The LNP-mRNA-G-H270P vaccine maintained its expected cellular immunity advantage, with the G+QS21+CpG group exhibiting moderately reduced but still significant levels of IFN-γ-secreting splenocytes and levels of IL-2 in the supernatant of spleen cells, as well as IFN-γ-producing CD4+ T cells. Both LNP-mRNA-G-H270P and G+QS21+CpG vaccine groups provided 100% protection against lethal challenge (50LD₅₀ RABV). Conclusions: These findings provide novel vaccine/adjuvant strategies for rabies while elucidating platform-specific immunogenicity patterns, offering critical insights for pathogens requiring balanced humoral/cellular immunity. Full article

Sunscreen protects skin from harmful Ultra Violet (UV) rays, preventing skin diseases like cancer and premature aging. This review explores the role of nanotechnology in enhancing sunscreen formulations by incorporating green and sustainable ingredients. Nanoparticles such as titanium dioxide and zinc oxide effectively reflect UV rays, improving protection while minimizing white residue, thereby enhancing aesthetics, stability, and efficacy. Recent advancements in formulation include lipid-based and polymer-based nanosystems that improve the delivery of active ingredients, offering multifunctional benefits. Additionally, modern sunscreens integrate anti-aging and antioxidant properties, reflecting the trend toward hybrid formulations with multiple skin benefits. The review also examines recent patents, highlighting innovations in nanotechnology-driven sunscreen formulations and delivery systems. Safety and regulatory concerns are critically analyzed, focusing on public perception of nanoparticles and their environmental impact. Issues such as manufacturing challenges and consumer hesitancy toward nano-scaled formulations due to safety considerations are also discussed. While nanotechnology presents significant potential in advancing sun protection, the review underscores the importance of balancing innovation with safety and sustainability. Ultimately, it serves as a guide for future research directions in nano-based sunscreens, advocating for responsible and informed development in the field. Full article

Phytochemicals exhibit a broad spectrum of pharmacological activities, including significant anticancer potential. However, their clinical translation is often hampered by poor aqueous solubility, low bioavailability, and chemical instability. Lipid-based nanocarriers, especially solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have proven to be effective strategies for addressing these challenges. These nanocarriers improve the solubility, stability, and bioavailability of phytochemical-based anticancer agents, while enabling controlled and tumor-specific drug release. Encapsulation of anticancer phytochemicals such as curcumin, quercetin, resveratrol, silymarin, and naringenin in SLNs and NLCs has demonstrated improved therapeutic efficacy, cellular uptake, and reduced systemic toxicity. Co-delivery strategies, combining multiple phytochemicals or phytochemical–synthetic drug pairs, further contribute to synergistic anticancer effects, dose reduction, and minimized side effects, particularly important in complex cancers such as glioblastoma, breast, and colon cancers. This review presents a comparative overview of SLNs and NLCs in terms of formulation methods, in vitro characterization, and classification of key phytochemicals based on chemical structure and botanical sources. The roles of these lipidic carriers in enhancing anticancer activity, challenges in formulation, and recent patent filings are discussed to highlight ongoing innovations. Additionally, hybrid lipid–polymer nanoparticles are introduced as next-generation carriers combining the benefits of both systems. Future research should aim to develop scalable, biomimetic, and stimuli-responsive nanostructures through advanced surface engineering. Collaborative interdisciplinary efforts and regulatory harmonization are essential to translate these lipid-based carriers into clinically viable platforms for anticancer phytochemical delivery. Full article

Background/Objectives: The development of a vaccine against highly pathogenic avian influenza viruses subtype A/H5 is an urgent task due to concerns about its pandemic potential. Methods: In this study, we have developed an experimental mRNA vaccine, mRNA-H5, encoding a modified hemagglutinin trimer of influenza virus A/turkey/Stavropol/320-01/2020 (H5N8). BALB/c mice were immunized with the mRNA-H5 vaccine using lipid nanoparticles (LNPs) and needle-free jet injection (JI). Subsequently, the immune response to vaccine was assessed using ELISA, microneutralization assay, and ICS methods, and a challenge study was conducted. Results: mRNA-H5 was shown to effectively stimulate specific humoral and T-cell immune responses. Moreover, mRNA-H5 delivered by LNPs and JI provided 100% protection of immunized mice against lethal challenge with homologous and heterologous strains of avian influenza virus (A/Astrakhan/3212/2020 (H5N8) and A/chicken/Magadan/14-7V/2022 (H5N1), respectively). Conclusions: The present results indicate that JI can be considered as an alternative to LNPs for mRNA delivery, and according to the literature, JI is safer than delivery using LNP. mRNA-H5 has potential as a vaccine against infection with highly pathogenic avian influenza A/H5 viruses with pandemic potential. Full article

We previously demonstrated lipid nanoparticle-mediated CRISPR-Cas9 gene editing to disrupt the gene encoding cytochrome P450 oxidoreductase (Cypor), combined with transient administration of acetaminophen (APAP), to repopulate the liver with healthy hepatocytes and rescue a phenylketonuria mouse model. This study aimed to investigate electroporation-mediated delivery of Cypor-targeting CRISPR-Cas9 ribonucleoproteins into wild-type hepatocytes, combined with liver engraftment under APAP treatment, as an in vivo selection approach in a mouse model of homozygous familial hypercholesterolemia (Ldlr^−/−). Electroporation provides higher delivery efficiency compared to lipid nanoparticles. We observed engraftment levels up to 13% engraftment of electroporated Cypor-deficient hepatocytes with indels in the liver of Ldlr^−/− mice after transient APAP administration, while negligible engraftment was observed in no-APAP controls (mean 9% and 2%, respectively, p = 0.0121). The engraftment of Cypor-deficient Ldlr^+/+ hepatocytes was associated with reductions in LDL-cholesterol (18%) and triglycerides (52%) compared to the untransplanted control Ldlr^−/− mice fed a Western diet for 5 weeks, but offered no protection from the development of diet-induced aortic root atherosclerosis or liver steatosis. While biochemical markers for liver damage normalized after discontinuation of APAP, we observed persistent lipid accumulation in the liver of Ldlr^−/− mice grafted with Cypor-deficient Ldlr^+/+ hepatocytes, likely stemming from the impact of Cypor deficiency on cholesterol clearance. Therefore, the combination of CRISPR-Cas9-mediated Cypor knockdown to induce clonal expansion of gene-edited hepatocytes using transient APAP administration is not a viable therapeutic strategy for familial hypercholesterolemia due to the essential role of Cypor in cholesterol metabolism. Unlike findings from phenylketonuria mouse model studies, the loss of Cypor function could not be compensated by unedited native hepatocytes in Ldlr^−/− mice. Collectively, our results demonstrate that electroporation is a viable and informative approach for evaluating gene editing strategies for the treatment of inherited metabolic diseases that affect the liver. Our electroporation procedure revealed that a one-size-fits-all gene editing strategy may not be universally applicable for treating inherited metabolic liver disorders. Tailored gene editing and selection strategies may be needed for different liver disorders. Full article

Messenger RNA (mRNA) vaccine technology has revolutionized the field of immunization, offering a non-infectious, non-genome-integrating platform that addresses many limitations of traditional vaccine modalities. Recent advancements in chemical modifications, delivery systems, and manufacturing processes have enhanced the stability, efficacy, and safety of RNA-based therapeutics, expanding their application beyond infectious diseases to include genetic disorders, cancer, and rare diseases. Central to the success of RNA vaccines is their ability to orchestrate a finely tuned immune response, leveraging both innate and adaptive immunity to achieve robust and durable protection. This review synthesizes current knowledge on the immunological mechanisms underpinning RNA vaccine efficacy, with a focus on the roles of pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) in sensing exogenous RNA, the impact of RNA modifications and manufacturing impurities on innate immune activation, and the subsequent cytokine and chemokine milieu that shapes adaptive responses. We also discuss the dual role of lipid nanoparticle (LNP) delivery systems as both carriers and adjuvants, highlighting their contribution to the vaccine’s immunogenicity and reactogenicity profile. Understanding these complex immune interactions is critical for optimizing RNA vaccine design, minimizing adverse effects, and expanding their therapeutic potential. This review aims to provide a comprehensive overview of the immune symphony orchestrated by RNA vaccines and to identify key areas for future research to further refine and expand the utility of this transformative technology. Full article

The concerning increase in respiratory infections that are resistant to multiple drugs has led to a growing interest in bacteriophage therapy as a potential alternative to conventional antibiotics. Effective phage delivery to the lungs, however, presents several formulation and stability issues, particularly for inhalation-based methods. This review highlights current developments in the creation of dry powder formulations that can be inhaled for pulmonary phage therapy, with a focus on encapsulation methods based on nanoparticles, such as solid lipid nanoparticles (SLNs) and polymer-based nanoparticles. These carriers enhance the aerodynamic characteristics of phages, making them suitable for deep lung deposition, while also protecting them during processing and storage. Several drying methods have been investigated to create powders with optimal morphologies, porosity, and dispersibility, including spray drying and spray freeze drying. The review also emphasizes how the phage morphotype affects stability, especially when nebulization stress is present. Furthermore, the advantages of nanoparticle matrices are confirmed by the reduced viability loss (usually< 0.5 log PFU) of encapsulated phages. Standardizing production processes, scaling up, and ensuring regulatory compliance remain challenging despite encouraging preclinical results. The combination of phage therapy with nanotechnology creates new avenues for the utilization of inhalable delivery methods to treat multidrug-resistant pulmonary infections. To translate these novel formulations from preclinical development to clinical application, sustained multidisciplinary collaboration across pharmaceutical sciences, microbiology, and clinical pharmacology is essential. Full article

Melanoma is a type of skin cancer with high lethality and increasing incidence. Current treatments typically involve surgery as the first step, followed by adjuvant treatments, which are necessary in most cases. These adjuvant treatments may include radiotherapy, phototherapy, chemotherapy, immunotherapy, and combined therapies. However, patients with melanoma still face great difficulties, such as the inefficiency of therapies and serious side effects, in addition to uncomfortable scars. Most of these problems are related to limitations of antitumor therapies, such as the low bioavailability of drugs, degradation in biological fluids, rapid clearance, difficulty in reaching the tumors, the low capacity for accumulation and infiltration in tumor cells, toxicity to healthy cells, and systemic action. Thus, antitumor therapy for melanoma remains a challenge. In this line, nanotechnology has brought new perspectives and has been the subject of intensive research on the use of nanoparticles (liposomes, lipid nanoparticles, polymeric nanoparticles, inorganic nanoparticles, carbon nanotubes, dendrimers, nanogels, and biomimetic nanoparticles, among others) as carriers for the controlled release of drugs and tumor diagnosis. This work outlines the main limitations of current melanoma therapies and explores how nanoparticle-based drug delivery systems can overcome these challenges, highlighting recent research and clinical developments. Full article

The therapeutic potential of cannabinoids and other ligands of cannabinoid receptors attracts considerable attention due to their diverse pharmacological effects and utility in various medical applications. However, challenges such as low solubility, limited bioavailability, and potential side effects hinder their broad clinical use. Nanoformulation techniques offer a promising approach to address these issues and optimize the therapeutic effectiveness of cannabinoids and other cannabinoid receptor ligands. This comprehensive review explores the advancements in nanoformulation strategies to enhance the therapeutic efficacy and safety of synthetic cannabinoids and related compounds, such as CB13, rimonabant, and HU-211, which have been studied in a range of preclinical models addressing conditions such as neuropathic pain, depression, and cancer. The review discusses various nanocarriers employed in this field, including lipid-based, polymeric, and hybrid nanoparticles, micelles, emulsions, and other nanoengineered carriers. In addition to formulation approaches, this review provides an in-depth analysis of chemical structures and their effect on compound activity, especially in the context of the affinity for the cannabinoid type 1 receptor in the brain, which is chiefly responsible for the psychoactive effects. The provided summary of research concerning either chemical modifications of existing cannabinoids or the creation of new compounds that interact with cannabinoid receptors, followed by the development of nanoformulations for these agents, allows for the identification of new research directions and future perspectives for Cannabis-based medicine. In conclusion, the combination of nanotechnology and cannabinoid pharmacology holds promise for delivering more effective and safer therapeutic solutions for a broad spectrum of medical conditions, making this an exciting area of research with profound implications for the healthcare and pharmaceutical industries. Full article

Background and Objectives: Over the past few years, there has been a significant shift in focus from developing better diagnostic tools to detecting Alzheimer’s disease (AD) earlier and initiating treatment interventions. This review will explore four main objectives: (a) the role of biomarkers in enhancing the diagnostic accuracy of AD, highlighting the major strides that have been made in recent years; (b) the role of neuropsychological testing in identifying biomarkers of AD, including the relationship between cognitive performance and neuroimaging biomarkers; (c) the amyloid hypothesis and possible molecular mechanisms of AD; and (d) the innovative AD therapeutics and the challenges and limitations of AD research. Materials and Methods: We have searched PubMed and Scopus databases for peer-reviewed research articles published in English (preclinical and clinical studies as well as relevant reviews and meta-analyses) investigating the molecular mechanisms, biomarkers, and treatments of AD. Results: Genome-wide association studies (GWASs) discovered 37 loci associated with AD risk. Core 1 biomarkers (α-amyloid Aβ42, phosphorylated tau, and amyloid PET) detect early AD phases, identifying both symptomatic and asymptomatic individuals, while core 2 biomarkers inform the short-term progression risk in individuals without symptoms. The recurrent failures of Aβ-targeted clinical studies undermine the amyloid cascade hypothesis and the objectives of AD medication development. The molecular mechanisms of AD include the accumulation of amyloid plaques and tau protein, vascular dysfunction, neuroinflammation, oxidative stress, and lipid metabolism dysregulation. Significant advancements in drug delivery technologies, such as focused Low-Ultrasound Stem, T cells, exosomes, nanoparticles, transferin, nicotinic and acetylcholine receptors, and glutathione transporters, are aimed at overcoming the BBB to enhance treatment efficacy for AD. Aducanumab and Lecanemab are IgG1 monoclonal antibodies that retard the progression of AD. BACE inhibitors have been explored as a therapeutic strategy for AD. Gene therapies targeting APOE using the CRISPR/Cas9 genome-editing system are another therapeutic avenue. Conclusions: Classic neurodegenerative biomarkers have emerged as powerful tools for enhancing the diagnostic accuracy of AD. Despite the supporting evidence, the amyloid hypothesis has several unresolved issues. Novel monoclonal antibodies may halt the AD course. Advances in delivery systems across the BBB are promising for the efficacy of AD treatments. Full article

Background: The bacterial wilt of tomatoes, caused by Ralstonia solanacearum, is a soil-borne plant disease that causes substantial agricultural economic losses. Various nanoparticles have been utilized as antibacterial agents to mitigate pathogenic destructiveness and improve crop yields. However, there is a lack of in-depth research on how nanoparticles affect tomato metabolite levels to regulate the bacterial wilt of tomatoes. Methods: In this study, healthy and bacterial wilt-infected tomatoes were treated with Cu-Ag nanoparticles, and a metabolomics analysis was carried out. Results: The results showed that Cu-Ag nanoparticles had a significant prevention and control effect on the bacterial wilt of tomatoes. Metabolomic analysis revealed that the nanoparticles could significantly up-regulate the expression levels of terpenol lipids, organic acids, and organic oxygen compounds in diseased tomatoes, and enhance key metabolic pathways such as amino acid metabolism, carbohydrate metabolism, secondary metabolite metabolism, and lipid metabolism. These identified metabolites and pathways could regulate plant growth and defense against pathogens. Correlation analysis between the tomato microbiome and metabolites showed that most endophytic microorganisms and rhizospheric bacteria were positively correlated with fatty acyls groups and organic oxygen compounds. Conclusions: This study reveals that Cu-Ag nanoparticles can actively regulate the bacterial wilt of tomatoes by up-regulating the levels of lipid metabolism and organic oxygen compounds, providing an important theoretical basis for the application of nanoparticles in agriculture. Full article